Recently, reaction liquids for use in analysis systems which measure the amounts of ingredients of a sample liquid have been required to be more minute quantities to reduce reagent cost and reduce environmental burdens. Current analysis systems dispense a sample liquid and a reagent into plastic or glass reaction solution vessels, mix them to prepare reaction solutions, and measure the amounts of ingredients by measuring the intensity of light emitted from or transmitted through the reaction solutions. When preparing more minute quantities of reaction solutions in the current analysis systems, the liquids become harder to handle and bubbles are generated during the dispensing and mixing process. This has posed a problem in which accurate measurements cannot be achieved. For this reason, techniques of microfluidic liquid handling with accuracy have been required.
As a technique of microfluidic liquid handling, a method that transports a liquid on a substrate under electrical control has lately attracted attention. In this method, generally the following two manners are used. A first manner is such that liquid droplets to be transported are sandwiched between two opposing substrates having a plurality of electrodes and the droplets are driven by applying voltage to electrodes arranged along the surfaces of the two opposing substrates (e.g., [patent document 1]). Typically, a great number of electrodes are arranged on one substrate along a fluid channel through which a liquid is allowed to move and the other substrate has a single electrode formed over its surface and connected to ground. When a liquid droplet stands still across some electrodes and voltage is applied to one of these electrodes under the droplet, the droplet in contact with the electrode to which the voltage is applied comes to have a good wetting behavior and eventually moves to just above that electrode by electrocapillarity (e.g., [patent document 2]). By repeating this, the droplet is transported.
Another manner is such that a liquid droplet to be transported is supplied to enter a channel on a single substrate with a great number of electrodes and the droplet is driven by applying voltage to an electrode near the droplet (e.g., [patent document 3]). The electrodes are arranged along the fluid channel through which a liquid is allowed to move. By forming an electric field between an electrode lying under the droplet and an electrode near the droplet and utilizing the force of the electric field, the droplet is driven. By repeating this, the droplet is transported.
Both these manners are capable of transporting microfluidic liquid. In these manners, by moving two microdroplets of liquids to a same electrode, the microdroplets can be mixed and it is also possible to divide one microdroplet into two parts. These systems in which a microfluidic liquid is transported and analyzed by switching one electrode to another to which voltage is applied on the substrate having an array of electrodes have the following advantages. Because a single or two substrates are used, samples are less liable to be affected by bubbles than a vessel with side walls. Simply applying voltage to the electrodes, a large number of microdroplets can be driven individually wherever on the substrate. Because a position in which a microdroplet is placed can be determined by applying voltage to a certain electrode, if measurement is performed by a measuring section provided to obtain information from a sample, timing when the sample droplet or reaction solution arrives at the measuring section can be set easily. Analysis systems devised and built by substrate technology have been reported (e.g., [non-patent document 1] and [non-patent document 2]).
In a typical example of analysis systems described in the above documents, there are a sample inlet section into which a sample droplet is inserted into the substrate, a mixing section where the sample liquid is mixed with a reagent, a measuring section for measurement, and an outlet section from which a reaction solution is ejected and these sections are connected by a fluid channel formed with a great number of electrodes. A sample liquid entered from the sample inlet section is mixed with a reagent in the mixing section and a reaction solution is prepared. After ingredients are measured in the measuring section, the reaction solution is transported back through the same fluid channel and ejected from the outlet section.
[Patent document 1] JP-A No. 216324/1985
[Patent document 2] JP-A No. 2004-000935
[Patent document 3] JP-A No. 267801/1998
[Patent document 4] JP-A No. 2004-22165
[Patent document 5] JP-A No. 267801/1998
[Non-patent document 1] R. B. Fair et al. “Electrowetting-based On-Chip Sample Processing for Integrated Microfluidics” IEEE Inter. Electron Devices Meeting 2003
[Non-patent document 2] Vijay Srinivasan et al. “Clinical diagnostics on human whole blood, plasma, serum, rine, saliva, sweat, and tears on a digital microfluidic platform” μTAS 2003
[Non-patent document 3] Eric Bakker, Philippe Buhlmann, and Erno Pretsch Chem. Rev. 1977, 97, 3083-3132